The human gut is a complex ecosystem harboring up to a 1000 different microbial species. It is now known that microbial diversity within the gut impacts human health and metabolism and it is hoped that the study of human microbial diversity will lead to novel medical treatments. The objective of this study is to characterize gut microbes sampled from people living in remote geographic areas. This objective can have a transformative impact on human microbiome research, especially the question of whether there is a "core human microbiome", meaning, some aspect of microbial genome diversity that all healthy people share. Yet, nearly all studies to date are limited to clinical samples from developed nations. These samples have an ascertainment bias because the natural state of human microbiome diversity is disrupted by medications such as antibiotics, and likely, introductions of microbes from global food resources. The proposed study is unique in that the samples to be studied lack this bias. Samples are to be analyzed using state of the art genome technologies, including a novel gene array. The specific aims are (AIM1) to collect fecal samples and record dietary information from three remote contemporary native Peruvian communities, each living in three very different environments: coastal desert, high-elevation Andean grasslands, and the Amazon jungle. In addition, one ancient community, where samples were retrieved from mummified remains, will be included. AIM2 is to characterize the bacterial species and bacterial genes observed in these samples using next generation genome sequencing and novel gene array technologies. AIM3 is to isolate key members of the microbial ecology. Hypotheses tested include: i) gut microbiomes are geographically structured, meaning the frequencies of microbial taxa and gene functions are more similar within a population than between populations. ii) microbiomes from remote communities have high species diversity. iii) newly recorded species of microflora are present within these remote ecologies. iv) microbes, atypical of gut ecologies in developed nations, assume functional roles within remote communities. Each of these hypotheses is a logical contribution to assessing human microbial diversity and the extent to which a core human microbiome exists. PUBLIC HEALTH RELEVANCE: Human microbial diversity is shown to impact human disease risks, drug metabolism, and may provide a foundation for novel drug treatments;yet, to date, the range of human microbial diversity is largely limited to observations from clinical samples from industrialized nations. This study will greatly expand the knowledge of human microbial diversity by using state of the art technology to characterize human microbes of the gut collected from contemporary remote indigenous communities living in three very different environments: coastal desert, high altitude Andes, and the Amazon jungle as well as ancient samples derived directly from mummified human remains.